TITLE Trisomy 9 Syndrome in an Infant with Ambiguous Genitalia •Authors Parastoo Rostami1, Maryam Nakhaeimoghadam1, Arya Sotoudeh1, Reihaneh Mohsenipour1, Nima Rezaei2,3,4 •1 Department of Pediatric Endocrinology, 2 Research Center for Immunodeficiencies, Children's Medical Center, 3Department of Immunology, School of Medicine, Tehran University of Medical Sciences, 3Universal Scientific Education and Research Network (USERN), Tehran, Iran OBJECTIVES Case report •The pericentric inversion of •The patient is a 4-month boy who was referred to the Children’s Medical Center, the Pediatrics Center of Excellence Chromosome 9 is the most common in Iran, because of ambiguous genitalia. There was no problem abnormality of human chromosomal after in mother pregnancy, while the fetal ultrasounds was also trisomy 21 and fragile x (1), which is normal during pregnancy. Birth weight was 3200 gram, length estimated to be seen up to 1-3 percent in 49 cm, and head circumference was 34 cm. He has normal general population (1-4). Although this growth and development. On physical examination, the chromosomal abnormality might not lead to external genitalia was ambiguous. There was small phallus, any clinical presentation in the most cases while palpaple gonads in scrotom was detected. He haD (5), several signs and symptoms have perinoscerotal hypospadiasis (Figure 1). Laboratory tests, such already been reported in some cases such as DHEAS (Dihydroepiandrostrone, 17OHP (Hydroxy progesterone), Andrestandione, sodium, potassium, cortiso l, as infertility, recurrent miscarriage, unusual ACTH were all normal. In HCG (Human Chorionic features and multiple congenital anomalies Gonadotropin) test, testosterone and dihydrotestostrone were (1,6-9). The clinical attribute of this increased after test (Testosterone and dyhydrotestostrone syndrome are growth and mental before test were 0.06 ng/ml and 22 pg/dl respectively, retardation, microcephaly, low-set ears, respectively; after test testosterone and dyhydrotestostrone upward-slanted eyes, wide sutures and were 5.5 ng/ml and 63 pg/ml, respectively). Echocardiography fontanelles, broad nose, congenital heart revealed VSD (venticular septal defect) with 5 mm diameter. defects, micrognathia, enophthalmos or Sonography of brain and kidney were normal. Karyotype was microphthalmos, abnormal brain, skeletal performed which showed 46, XY, inv (9) (p12; q13) (Figure 2). His mother’s Karyotype was 46, XX, inv (9) (p12; q13), while and urogenital abnormalities and external the father’s was 46, XY. genitalia ambiguous (8,10). Discussion •In this study, a case with ambiguous genitalia was presented that the sex determination after the chromosomal analysis revealed 46 XY, trisomy 9 inv(p12,q13). The chance of structural abnormalities of autosomes or sex chromosomes in new born infants is about 0.5% (11). The most common and known chromosomal abnormality are trisomy 21 and the fragile X syndromes (1). Pericentric inversions could be occurred in all chromosomes, except chromosome 20 (6). It seems that the chromosome 9 is susceptible to breakage, and this could be the reason that inversion 9 could occur commonly (12). The incidence of inv(9) is higher in females fetuses than males fetuses (7:1) (9). Inv(9) could be associated with different clinical conditions such as children with dysmorphic features and with repeated spontaneous abortions. Previous reported showed that inv (9) was detected in patients with various congenital anomalies such as in central nervous system, heart, and kidney (1,9,13-16), but our patient just had VSD with diameter 5 mm in echocardiography (13-17). Inv(9) in children is associated with dysmorphic features and some symptoms such as growth and mental retardation, low-set malformed ears, microcephaly, wide sutures and fontanelles, upward-slanted eyes, small palpebral fissures, enophthalmos or microphthalmos, broad nose with bulbous tip, micrognathia, abnormal brain, congenital heart defects, skeletal and urogenital abnormalities (6,18). However our case had got normal features (1,13). Abnormal ambiguity include hypospadias, micropenis and cryptorchidism were previously reported in trisomy 9inv (p12,q13) (14,15,17). The presented case here had also genital ambiguity such as micropenis, hypospadias, and bifid scrotum. •Trisomy 9 syndrome could be considered in the list of differential diagnosis of those with ambiguous genitalia. Chromosomal karyotype and culture could be recommended in children with ambiguous genitalia, while parental chromosomal analysis is necessary for genetic counseling References 1. Rao BV, Kerketta L, Korgaonkar S, Ghosh K. Pericentric inversion of chromosome 9[inv(9)(p12q13)]: Its association with genetic diseases. Ind J Hum Genet 2006;12(3):129-132. •2. Ait-Allah A, Ming P, Salem H, et al. The clinical importance of pericentric inversions of chromosome 9 in prenatal diagnosis. J Matern Fetal Invest. 1997;7:126-128. •3. Teo SH, Tarn M, Knight L, Ng I. Pericentric inversion 9-incidence and clinical significance. Ann Acad Med Singapore 1995;24:302 •4. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, et al . DNA sequence and analysis of human chromosome 9. Nature 2004;429(6990):369-74 •5. Gardner RJ, Sutherland G. In: Chromosomal Abnormalities and Genetic Counseling. 3rd ed. New York: Oxford University Press; 2004. •6. Srebniak M, Wawrzkiewicz A, Wiczkowski A, et al. Subfertile couple with inv(2),inv(9) and 16qh+. J Appl Genet. 2004;45:477-479. •7. Feingold M, Atkins L. A case of trisomy 9. J. Med. Genet. 1973;10(2):184-7. •8. Abu Henedi MM, Mohammed FM, Masoud HA, Abualhasan SJ, Al Awadi SA. Trisomy 9 syndrome in a neonate with unusual feature. Egypt J Med Hum Genet 2009;10(2). •9. Jeong SY, Kim BY, Yu JU. De Novo Pericentric inversion of chromosome 9 in congenital anomaly. Yonsei Med J 201051(5):775–780 •10. Tarani L, Colloridi F, Raguso G, RizzutiA, Bruni L, Tozzi MC, et al. Trisomy 9 mosaicism syndrome. A case report and review of the literature. Ann.Genet. 1994;37(1):14-20. Baltaci V, Ors R, Kaya M, Balci S. A case associated with Walker Warburg syndrome phenotype and homozygous pericentric inversion 9: coincidental finding or aetiological factor? Acta Paediatr 1999;88:579–583 •17. Sandoval R, Sepulveda W, Gutierrez J,Be C, Altieri E. Prenatal diagnosis of nonmosaic trisomy 9 in a fetus with severe renal disease. Gynecol. Obstet Invest 1999;48(1):69-72. •18. Ashrafzadeh F, Faraji M, Goldenhar syndrome and pericentric inversion of chromosome 9. Iran J Med Sci 2006; 31(2). •15. Kor Anantakul O, Suwanrath C, Kanngurn S, Rujirabanjerd S, SuntharasajT, Pinjaroen S. Prenatal diagnosis of complete trisomy 9: A case report and review of the literature. Am J Perinatol 2006;23(2):131-5 •1. Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger JQ. Malformations in newborn: Results based on 30,940 infants and fetuses from Mainz congenital birth defect monitoring system (1990-1998). Arch Gynecol Obstet 2002;266:163- 65 •12. 441--P2 Gonads & DSD Poster presented at: 55ESPE 55ESPE parasto rostami DOI: 10.3252/pso.eu.55ESPE.2016.